Many workers have attempted to develop an effective and practical chemotherapeutic regimen for brucellosis in animals, including humans, and particularly in dairy animals such as camels, cows, sheep and goats. The goal has been to salvage farm animals with superior production and breeding potential. Furthermore in many countries the slaughter of infected animals is not possible for financial reasons and healthy replacements may not be available. Clearly, a short term treatment regimen would be of major benefit to animal husbandrymen world wide. Furthermore, infected animals are a vector for the infection of humans using contaminated dairy products.
It is known that in vitro intraphagocytic killing of Brucella abortus in bovine mononuclear leukocytes was enhanced by multilamellar liposomes containing the aminoglycoside gentamicin. Dees, C., et al., "Enhanced Intraphagocytic Killing of Brucella abortus in Bovine Mononuclear Cells by Liposomes Containing Gentamicin", Vet. Immunol. and Immunopath, 8:171-182 (1985). In vitro killing of Brucella abortus was also enhanced when compared to free gentamicin. Other studies found that stable plurilamellar vesicle-entrapped aminoglycosides administered to Brucella canis infected mice and Brucella abortus infected guinea pigs effectively eliminated bacteria from the organs. Fountain, M. W., et al, "Treatment of Brucella canis and Brucella abortus in Vitro and in Vivo by Stable plurilamellar Vesicle-Encapsulated Aminoglycosides", J. Inf. Dis., 152:529-535 (1985).
Recent studies found that a combination of a long-acting tetracycline such as oxytetracycline (e.g., LA-200.TM., Pfizer, Terra haute, IN) and streptomycin apparently cured 67% of infected dairy cows. Milward, F. W., "Effectiveness of Various Therapeutic Regimens for Bovine Brucellosis", Am. J. Vet. Res., 45:1825-88 (1984); Nicoletti, P. W., "Efficacy of Long-Acting Oxytetracycline Alone or Combined with Streptomycin in the treatment of Brucellosis", Vet. Med. Assoc, 187:493-95 (1986). Other studies indicated that extension of treatment improved the cure rate to over 90%. However the treatment regimen required was both lengthy and laborious, requiring approximately one month maintainence of therapeutically effective levels of antibiotic in tissue. Therefore, attempts have been made to reduce the length and difficulty of treatment and increase the efficiency of the antibiotics employed.
Treatment of pathological mammary conditions has been beset with the problem of administering therapeutically effective levels of therapeutic agent into the mammary tissue with special reference to the lymphatic system serving the mammary gland, the proximal mammary lymph nodes. Infections and neoplasms of mammary tissue and proximal lymph nodes have proved resistant to treatment.